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With eight million deaths in 2012 lung cancer is the most common cause of cancer death in the world, and the problem is still growing. As long as the goal of a total ban on smoking tobacco is not fulfilled, lung cancer screening as a means of secondary prevention has great potential. The aim of lung cancer screening is the detection of lung cancer in an early and hopefully curable stage resulting in a significant reduction in lung cancer deaths in the population. The Dutch Belgium lung cancer screening trial (NELSON), that included 15822 participants is the largest in Europe. The results of this trial, aiming at a reduction of the lung cancer mortality rate of 20%, are expected in 2015 or 2016. This thesis focuses on SubSolid Nodules (SSNs), a special kind of nodules that pose a growing problem in lung cancer screening. SubSolid Nodules are also referred to as Ground Glass Opacities (GGO) or Ground Glass Nodules (GGN). In this term ground glass is defined as a circumscribed area of increased lung attenuation with preservation of the bronchial and vascular margins. The problems with SSNs compared to solid nodules are in part inherent to the appearance of the nodules: SSNs are less dense and less well circumscript and thus not only harder to see on the image but also more difficult to measure accurately compared to solid nodules. The second problem with SSNs that makes them more difficult to handle codes comes the fact that their biological behavior is different from SSNs. Therefore a verdict of malignancy by the pathologist does not necessarily mean that the patient will benefit from treatment of that nodule. In this thesis we tried to make a contribution towards the solution of these problems by: • reporting on the possible improvement of the visual detection of SSNs • investigating several aspects of the semi-automatic segmentation of SSNs • investigating the feasibility of the segmentation of a solid component in a SSN • investigating a more conservative approach compared to present recommendations in managing SSNs. • evaluating the radiological aspect of missed carcinoma’s in the NELSON trial. Overall conclusions. In this thesis we have demonstrated that semi-automatic segmentation of SSNs and its solid component is achievable with sufficient accuracy in an efficient manner. The restrained NELSON approach of SSNs has not lead to any interval or post screen carcinoma in the investigated follow up period. Furthermore we have shown that although interval or post screen carcinomas due to human errors are rare, there is room for improvement in the detection of intra bronchial lesions and that at present still a lot has to be learned about the significance of focal bulla wall thickening. However, even by demonstrating that the more restrictive NELSON approach of SSNs is to be preferred over the current recommendation, we still don’t know what the biological behavior of SSNs is, and consequently what would be the optimal screening or therapeutic strategy in these cases. Therefore several challenges still have to be met to optimize the strategy of lung cancer screening.

OBJECTIVE. CBCT-guidance (CBCT-guidance) is a new stereotactic technique for needle interventions, combining 3D soft-tissue cone-beam CT, needle planningsoftware, and real-time fluoroscopy. Our objective was to evaluate the use, feasibility and outcome of this technique. To determine the effective dose for the patient and operator during these procedures and to use the merging modality of this sytems is to quantify the kidney movement by transfer the patient from supine to prone position. MATERIALS AND METHODS. All procedures were performed using a flat-panel based fluoroscopy-system capable of acquiring cone-beam CT-images with dedicated needle path planning software. In the data set, a needle trajectory is determined and, after co-registration, a fusion image is created from fluoroscopy and a slice from the data set, enabling the needle to be positioned in real-time. In a spine phantom we analyzed the outcome of randomized CBCT-guidance and fluoroscopy-guided vertebroplasty procedures. Another phantom was used to compare CBCT-guidance and CT-guidance for inplane, angulated and double angulated needle paths. Multiple studies were performed to evaluate CBCT-guidance in clinical setting (e.g. general (N=145), lungbiopsies (N=84), kidneybiopsies (N=41), type-II endoleak treatment (N=5)). Based on 92 procedures the patient dose was calculated and compared to the dose of 137 CT-guided procedures. The operator dose (hand, collar and gonad region) was measured in a model and during clinical casus. Leaddrapes and ceiling/couch-shielding were used to measure the effect of shielding. By merging a supine-CT with a prone-CBCT the needle planningsoftware was used to determine the movement of the kidney. RESULTS. The mean accuracy using CBCT-guidance is 93%. All procedures have a 100% technical success. The mean proceduretime is 25.2 minutes and the fluoroscopytime is 169.5 seconds. CBCT-guidance has a significant better accuracy then fluoroscopy. Compared to CT-guidance, CBCT-guidance has a significantly better accuracy in complex procedures. The mean outcome for sensitivity, specificity, PPV, NPV, and accuracy was 90.9%, 100%, 100%, 78.1%, and 93.4% respectively. Total mean effective doses with cone-beam CT guidance was between 7.6-16.1 depending of the anatomical location. Effective doses with CT-guidance was 13.0-20.4 mSv. CBCT-guidance results in a significant effective dose reduction of 13%–42%. The mean doses for the hand were 34.2 and 54.6 µSv (thoracic/abdominal respectively). The doses for thyroid and gonad regions were 83.2 and 34.3 µSv in the thoracic, and 66.2 and 47.2 µSv in the abdominal group. Combined shielding reduced dose by 98.2-98.9% (p

In Chapter 1, an outline of the thesis is given. In Chapter 2 we concluded that most conservatively treated patients with VCFs had sufficient pain relief during the first 3 months. After one year a substantial proportion of patients still had disabling pain despite higher class pain medication used. There were no predictors for the development of chronic pain. In Chapter 3 we concluded that pulmonary PMMA embolism during PV is an infrequent complication without clinical sequelae. After one year, no pulmonary reaction is seen on CT. No definite relationship of PMMA emboli with injected cement volume could be established. In Chapter 4 we concluded that small and clinically silent PCE occurred in a quarter of patients treated with PV. Cement leakage into the azygos vein was the only risk factor.Over time, these small cement emboli remained inert without inflammatory pulmonary response. In Chapter 5 we concluded that perivertebral cement leaks during PV for osteoporotic vertebral compression fractures occurred frequently. Cement leakage occurred more frequently with higher injected volumes. All patients remained asymptomatic and late cement migration during follow-up did not occur. Standard post-procedural CT of the treated vertebral body in PV is not necessary. In Chapter 6 we concluded that for a substantial proportion of patients local anesthesia was not sufficient for pain reduction during PV. The severity of pain experienced by the patient is mostly not valued correctly by the operator. In Chapter 7 we concluded that clinical response of percutaneous vertebroplasty is not affected by differences in injected cement volume. There is no correlation between injected cement volume and fracture location, fracture severity and type of treated vertebra. In Chapter 8 we concluded that the incidence of new vertebral compression fractures was not different after PV compared with conservative therapy after 1 year follow-up. Only risk factor for new vertebral compression fractures was the number of vertebral compression fractures at baseline. PV contributed to preservation of stature by decreasing both incidence and severity of further height loss in treated vertebra.In Chapter 9 the results of the different aspects of percutaneous vertebroplasty are interpreted and discussed.